Colket Translational Research Building integrates medicine, informatics, and future technologies

The Colket Translational Research Building (CTRB) at the Children's Hospital of Philadelphia (CHOP) represents a fresh approach to one of the most challenging aspects of the medical research culture: bringing clinicians and investigators together to work in an effective collaborative environment.

“The mission of CHOP is to advance the health of children by turning scientific discovery into medical innovation,” says Tom Curran, Ph.D., Deputy Scientific Director at the Children’s Hospital of Philadelphia Research Institute. “We need to push beyond the existing interfaces between basic and clinical research. That is why we really want to promote integration, communication, collaboration, and cooperation among investigators.”

The 773,011-square-foot building groups occupants according to research theme instead of by traditional departmental or divisional affiliation. The resulting transdisciplinary hubs, referred to as "centers of emphasis," place physicians and researchers in interconnected fields in close proximity, with the intent of accelerating the flow of scientific advances from the bench top to the bedside.

The state of the art facility incorporates structural and design features that achieve efficiencies in space and energy utilization. Along with housing several state-of-the-art facilities like a genomics research center and the first-ever biorepository for pediatric research, the Colket Building also incorporates structural and design features that achieve efficiencies in space and energy utilization. LEED Silver certification is anticipated. An external utilities plant and exterior Super-X bracing free up internal real estate for more procedure rooms and support space. Working service corridors are extra wide to accommodate noisy, heavy equipment without interfering with pedestrian circulation. An L-shaped sidesaddle mechanical space for the vivarium affords more protection and better access control than an interstitial service scheme.

First occupied in 2008, the building currently encompasses four floors below grade and 11 above. CHOP is planning to build an additional 11 floors on top of the existing structure, but has not yet scheduled the construction.

The basement levels house a large animal vivarium, rodent facilities, a shelled rodent floor, support space and research core facilities including a High Throughput Sequencing Core, and a biorepository dedicated to the storage of biological materials (primarily DNA).

The first two above-ground floors are dedicated to the lobby, cafeteria, administration, and conference facilities. The three centers of emphasis follow: the Childhood Cancer Center on floors three and four, the Cell and Gene Therapy Center on five, and the Mitochondrial Center on six.

The three centers of emphasis follow: the Center for Childhood Cancer Research, on floors three and four; the Center for Cellular and Molecular Therapeutics, on five; and the Center for Mitochondrial and Epigenomic Medicine, on six. Two floors of mechanical space occupy floors seven and eight. The remaining three floors are built to laboratory specifications but are temporarily fitted with office cubicles.

Animal facility

Translational research imposes a host of new facilities demands. For one thing, an integrated vivarium is key for the kinds of studies that take place in the research center. Other important trends that must be accommodated are the increase in hospital-like treatment and procedures, and the growing dependence on transgenic animals, requiring more stringent pathogen control.

“Animal facilities used to be primarily holding facilities, like a hotel for mice,” Curran says. “That is not the case anymore. They now have to come with a whole series of core structures and essentially an animal hospital, because now we treat the rodents very similarly to the way we treat our patients.”

Three different types of core structures are embedded in the rodent vivarium: imaging, behavior, and transgenics.

The high-end multimodal imaging suite houses many of the same devices—ultrasound, MRIs, micro-CTs, and PET scanners—used to treat human patients. The control interfaces are also similar, making them easier for clinicians to work with. For example, the newest MRI for rodents has the same kind of software interface as the one in the main hospital, Curran points out.

The one drawback to the suite is a lack of growing room.

“If there was one area where I think we should have added more space, it is probably here, because new technologies keep coming out to allow us to do non-invasive imaging of responses to new therapeutics,” he says.

The extensively used behavior suite houses a wide array of animal behavior testing equipment. For maximum flexibility, the equipment is easy to reconfigure, remove, upgrade, or replace.

The proliferation of genetically modified animals is accompanied by the critical need for pathogen control. Bolstering the protection afforded by traditional measures, such as clean/dirty corridors, sterilizing incoming equipment, and electronic access controls, CTRB located the transgenic facility in the furthest, cleanest end of the building.

The sidesaddle mechanical, plumbing, and electrical scheme is another protective strategy. Keeping the MEP infrastructure outside the main core of the vivarium has many advantages over an interstitial arrangement.

“We put most of the MEP controls for the animal facility off to the side,” says Howard Eck, CHOP Director of Research Resources. “If equipment goes down, facilities personnel do not have to enter the animal perimeter. This helps maintain its integrity. The sidesaddle also affords free, unfettered access to the systems needing repair or replacement. Maintenance staff have headroom so they don't have to crawl over ceiling tiles. They can work on full-size systems in fully functional elevated space.”

Biorepository

In addition to being the first of its kind in pediatric research, the CTRB's cutting-edge biorepository is one of the first such facilities overall to be equipped with onsite automated DNA storage.

“Research on human specimens really can’t begin until you have an inventory of biospecimens,” Curran explains. “The best way to build critical mass is to spend five years collecting and preserving biospecimens. Then they can be provided as a collection for others to work with.”

The biorepository presents several demanding requirements for storage, both for physical materials and the associated data in electronic format. The controlled environment is provided by a minus-20 degree Centigrade automated robotic freezer with a capacity of up to 2 million specimens. Tied into the lab information management system is the industrial-scale robotic retrieval scheme, which is also integrated with inventory control and metadata. Researchers place their requests for biospecimens online. The robot picks the appropriate samples by barcode and then moves them to a transfer area for delivery to the lab the next day.

The super-flat floor required for the robotic tracks posed a major construction challenge. System specifications mandated a maximum floor variation of one millimeter across a one-meter length.

“It was hard to find a contractor able to work to this degree of precision,” Curran says.

CHOP submitted an application to fund the biorepository robotics system to the National Institutes of Health as an S10 grant under the American Reinvestment and Recovery Act in May 2009 The grant was not awarded, but the hospital went ahead with the purchase nevertheless.

“It was so important for the future of our research that we decided to find the resources and build it anyway,” Curran says. “I would encourage people to think about integrating biospecimen collection and annotation within the research environment in any new facility under consideration.”

Along with the biospecimens comes the need to analyze them. CTRB purchased eight high-end next-generation sequencers to perform the function onsite. Curran says a debate exists within the research community on whether institutions should run their own sequencing operations or outsource the work to a specialty group. While the sequencers are expensive and must be housed in a room with its own temperature and humidity control, he notes that they are not cost prohibitive.

What is more important for the research center is the opportunity to develop its own sequencing expertise, especially in the area of informatics. The up-and-coming emphasis on the whole-genome sequencing approach is undeniable.

“We envisage a time when every patient coming into CHOP will have his or her entire sequence determined,” Curran says. “The best way to develop your expertise in informatics is to have your own pipeline of sequence information coming out.”

The vast amount of information that sequencing generates, along with the need to store it, is a challenge institutions should get used to. To lessen the strain on its IT capabilities, CTRB is adding a core area where the sequence data is put in temporary storage for initial processing and winnowing before being uploaded to the storage area network. In addition, CTRB will have redundant storage facilities at two different geographic locations with a capacity of up to one petabyte.

“This research IT is actually teaching the hospital how to deal with large amounts of information as well as confidential information,” Curran says. “We have a large clinical database of information tied to these sequence arrays that will just continue to grow over time. In terms of technologies, we view this as fundamental to the future growth of translational research.”

Lab features

Laboratory floors are characterized by an increased amount of support space, reflecting the growing presence of dedicated equipment and the expanding need for special purpose rooms. Each of the 23 research bays per floor has a small alcove for lab support, supplemented by an array of different size rooms—for procedures, microscopes, cold rooms, for example—along the inner core. The labs themselves, designed for flexibility, are furnished with removable and height-adjustable freestanding wall benches and wheeled casework.

Further large equipment and supplemental storage space is supplied by a 12-foot-wide working corridor, a special feature. In contrast to some institutions that discourage the placement of equipment in service corridors, CTRB promotes the practice as a good way to get potentially disruptive heat- and noise-generating devices out of the lab. Open to the slab above, the corridor height is 16 feet, providing more storage space on shelving that runs high up on the walls.

A highlight of the fifth-floor Cell and Gene Therapy Center is a GMP-like facility placed in close proximity to the investigators who are doing cutting-edge research developing new biologics. A restricted area with gowning requirements and stringent environmental controls, the embedded core serves as a step-up and testing area for the new products undergoing clinical trials.

“We already have a GMP production facility in another building,” Eck says. “The Colket space integrates the generation and testing of new biologics before they are sent to production, helping to facilitate the moving of concepts through the GMP process.”

Members of the production staff who work in the other facility have offices located in the Colket Building, where they can mix with the research staff.

Offices

Available in several configurations, offices are located at the front of the building. A generous ratio of offices to labs (a total of 28, six of them designed for sharing) not only fosters the integration of wet lab and dry lab staff, but also provides additional space for ancillary specialists, such as informatics scientists and clinical coordinators who need to be close to the research environment.

“This is where I bump into the clinicians accidentally,” Curran says. “Returning from the clinic, they start to tell me about a patient or a specific issue that triggers an idea for a project in the lab. The corridor is working as intended.”

Designated lounge areas also help promote interaction among building occupants, and an assortment of conference and meeting rooms can accommodate groups of up to 180 people.

“We are very grateful to the Colket family, who has been supporting Children’s Hospital through three generations. Their initial donation was instrumental in getting this wonderful new facility constructed,” Eck says.